Default mode network connectivity and cognition in the aging brain: the effects of age, sex, and APOE genotype.

Andrea T. Shafer; Lori Beason-Held; Yang An; Owen A. Williams; Yuankai Huo; Bennett A. Landman; Brian S. Caffo; Susan M. Resnick

doi:10.1016/j.neurobiolaging.2021.03.013

Default mode network connectivity and cognition in the aging brain: the effects of age, sex, and APOE genotype.

Andrea T. Shafer, Lori Beason-Held, Yang An, Owen A. Williams, Yuankai Huo, Bennett A. Landman, Brian S. Caffo, Susan M. Resnick

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

The default mode network (DMN) overlaps with regions showing early Alzheimer's Disease (AD) pathology. Age, sex, and apolipoprotein E ɛ4 are the predominant risk factors for developing AD. How these risk factors interact to influence DMN connectivity and connectivity-cognition relationships before the onset of impairment remains unknown. Here, we examined these issues in 475 cognitively normal adults, targeting total DMN connectivity, its anticorrelated network (acDMN), and the DMN-hippocampal component. There were four main findings. First, in the ɛ3 homozygous group, lower DMN and acDMN connectivity was observed with age. Second, sex and ɛ4 modified the relationship between age and connectivity for the DMN and hippocampus with ɛ4 vs. ɛ3 males showing sustained or higher connectivity with age. Third, in the ɛ3 group, age and sex modified connectivity-cognition relationships with the oldest participants having the most differential patterns due to sex. Fourth, ɛ4 carriers with lower connectivity had poorer cognitive performance. Taken together, our results show the three predominant risk factors for AD interact to influence brain function and function-cognition relationships.

Original language	English (US)
Pages (from-to)	10-23
Number of pages	14
Journal	Neurobiology of aging
Volume	104
DOIs	https://doi.org/10.1016/j.neurobiolaging.2021.03.013
State	Published - Aug 2021

Keywords

Aging
Apolipoprotein
Cognition
Connectivity
Default mode network

ASJC Scopus subject areas

General Neuroscience
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2021.03.013

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title = "Default mode network connectivity and cognition in the aging brain: the effects of age, sex, and APOE genotype.",

abstract = "The default mode network (DMN) overlaps with regions showing early Alzheimer's Disease (AD) pathology. Age, sex, and apolipoprotein E ɛ4 are the predominant risk factors for developing AD. How these risk factors interact to influence DMN connectivity and connectivity-cognition relationships before the onset of impairment remains unknown. Here, we examined these issues in 475 cognitively normal adults, targeting total DMN connectivity, its anticorrelated network (acDMN), and the DMN-hippocampal component. There were four main findings. First, in the ɛ3 homozygous group, lower DMN and acDMN connectivity was observed with age. Second, sex and ɛ4 modified the relationship between age and connectivity for the DMN and hippocampus with ɛ4 vs. ɛ3 males showing sustained or higher connectivity with age. Third, in the ɛ3 group, age and sex modified connectivity-cognition relationships with the oldest participants having the most differential patterns due to sex. Fourth, ɛ4 carriers with lower connectivity had poorer cognitive performance. Taken together, our results show the three predominant risk factors for AD interact to influence brain function and function-cognition relationships.",

keywords = "Aging, Apolipoprotein, Cognition, Connectivity, Default mode network",

author = "Shafer, {Andrea T.} and Lori Beason-Held and Yang An and Williams, {Owen A.} and Yuankai Huo and Landman, {Bennett A.} and Caffo, {Brian S.} and Resnick, {Susan M.}",

note = "Funding Information: The authors report no conflicts of interest. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = aug,

doi = "10.1016/j.neurobiolaging.2021.03.013",

language = "English (US)",

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T2 - the effects of age, sex, and APOE genotype.

AU - Shafer, Andrea T.

AU - Beason-Held, Lori

AU - An, Yang

AU - Williams, Owen A.

AU - Huo, Yuankai

AU - Landman, Bennett A.

AU - Caffo, Brian S.

AU - Resnick, Susan M.

N1 - Funding Information: The authors report no conflicts of interest. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Publisher Copyright: © 2021

PY - 2021/8

Y1 - 2021/8

N2 - The default mode network (DMN) overlaps with regions showing early Alzheimer's Disease (AD) pathology. Age, sex, and apolipoprotein E ɛ4 are the predominant risk factors for developing AD. How these risk factors interact to influence DMN connectivity and connectivity-cognition relationships before the onset of impairment remains unknown. Here, we examined these issues in 475 cognitively normal adults, targeting total DMN connectivity, its anticorrelated network (acDMN), and the DMN-hippocampal component. There were four main findings. First, in the ɛ3 homozygous group, lower DMN and acDMN connectivity was observed with age. Second, sex and ɛ4 modified the relationship between age and connectivity for the DMN and hippocampus with ɛ4 vs. ɛ3 males showing sustained or higher connectivity with age. Third, in the ɛ3 group, age and sex modified connectivity-cognition relationships with the oldest participants having the most differential patterns due to sex. Fourth, ɛ4 carriers with lower connectivity had poorer cognitive performance. Taken together, our results show the three predominant risk factors for AD interact to influence brain function and function-cognition relationships.

AB - The default mode network (DMN) overlaps with regions showing early Alzheimer's Disease (AD) pathology. Age, sex, and apolipoprotein E ɛ4 are the predominant risk factors for developing AD. How these risk factors interact to influence DMN connectivity and connectivity-cognition relationships before the onset of impairment remains unknown. Here, we examined these issues in 475 cognitively normal adults, targeting total DMN connectivity, its anticorrelated network (acDMN), and the DMN-hippocampal component. There were four main findings. First, in the ɛ3 homozygous group, lower DMN and acDMN connectivity was observed with age. Second, sex and ɛ4 modified the relationship between age and connectivity for the DMN and hippocampus with ɛ4 vs. ɛ3 males showing sustained or higher connectivity with age. Third, in the ɛ3 group, age and sex modified connectivity-cognition relationships with the oldest participants having the most differential patterns due to sex. Fourth, ɛ4 carriers with lower connectivity had poorer cognitive performance. Taken together, our results show the three predominant risk factors for AD interact to influence brain function and function-cognition relationships.

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KW - Default mode network

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Default mode network connectivity and cognition in the aging brain: the effects of age, sex, and APOE genotype.

Abstract

Keywords

ASJC Scopus subject areas

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